Short Bowel Syndrome GLP-2 Drug Pipeline — PatSnap Eureka
Short Bowel Syndrome & GLP-2 Analog Drug Pipeline
From teduglutide to glepaglutide, apraglutide, and next-generation circRNA biologics — explore the full patent and clinical landscape for GLP-2 receptor agonists in intestinal rehabilitation for SBS and related GI rare diseases.
GLP-2 Receptor: The Central Driver of Intestinal Rehabilitation
Short bowel syndrome (SBS) is a rare, life-threatening malabsorption disorder resulting primarily from surgical resection of the small intestine, leaving patients dependent on parenteral nutrition (PN) or parenteral support (PS) for survival. Causative conditions include Crohn's disease, mesenteric infarction, intestinal volvulus, trauma, congenital anomalies, and radiation-induced strictures — all leading to malnutrition, dehydration, and PN dependence.
The primary molecular target across all retrieved patent results is the GLP-2 receptor (GLP-2R) — a class B G protein-coupled receptor expressed in enteroendocrine cells, intestinal neurons, and subepithelial myofibroblasts of the stomach, small intestine, and colon. As documented by NIH-indexed GLP-2 receptor biology literature, GLP-2R agonism drives: crypt stem cell proliferation and villus elongation; inhibition of enterocyte and crypt apoptosis; enhancement of intestinal hexose transport; reduction of gastric acid secretion; improvement of intestinal barrier function and tight junction integrity; and increased intestinal blood flow.
A critical pharmacokinetic liability defines the entire drug class: native GLP-2 has a plasma half-life of approximately 7 minutes, because DPP-IV cleaves it at the Ala2-Asp3 bond to yield essentially inactive GLP-2(3–33). DPP-IV resistance is therefore the foundational chemical design objective for all SBS-approved GLP-2 analogs. Secondary indications referenced in the dataset include inflammatory bowel disease, radiation-induced enteritis, chemotherapy-induced mucositis, and renal/hepatic dysfunction secondary to PN dependence.
Seven Distinct GLP-2 Analog Drug Classes in the SBS Pipeline
From approved first-generation peptides to circular RNA biologics — the patent landscape reveals a rapidly diversifying toolkit for intestinal rehabilitation, as analysed via PatSnap's IP analytics platform.
DPP-IV-Resistant Substituted Peptides
The prototypic compound is teduglutide ([hGly2]GLP-2, where Ala-2 is replaced by Gly), approved under the trade names Gattex (US) and Revestive (Europe) for SBS treatment. This foundational substitution extends plasma half-life from ~7 minutes to ~2 hours by blocking DPP-IV cleavage at position 2. Assignees: NPS Allelix Corp., 1149336 Ontario Inc.
Approved: Gattex / RevestiveLong-Acting Structurally Optimized Analogs
Glepaglutide (ZP1848) by Zealand Pharma A/S incorporates substitutions at positions 8, 16, 24, and/or 28, with optional deletions at positions 31–33, enabling weekly dosing. It has been evaluated in Phase 3 EASE SBS 1 (NCT:03690206) and EASE SBS 2 (NCT:03905707) trials, where a subpopulation achieved complete independence from parenteral support. Apraglutide (VectivBio AG) represents a second compound in this class.
Phase 3: EASE SBS 1 & 2GLP-2 Fusion Proteins & Peptibodies
Shire-NPS Pharmaceuticals (now Takeda) has developed fusion proteins combining GLP-2 (including teduglutide) with the Fc region of an immunoglobulin — "peptibodies" with defined amino acid sequences (SEQ ID NO: 2–16, including B264 and K274). The Fc fusion format extends half-life beyond the ~2 hours of teduglutide. Indications include SBS, enterocutaneous fistula, GI radiation damage, and obstructive jaundice.
Perioperative & chronic SBSCircular RNA (circRNA)-Encoded GLP-2 Biologics
The most structurally novel modality in this dataset: a circular polyribonucleotide encoding a GLP-2 polypeptide or analog, combined with a half-life extension moiety and secretion signal sequence (Miller, Russell; WO, 2025). Targets include SBS, SBS-IF, pediatric SBS, adult SBS, major small bowel resection, and TPN-induced intestinal mucosal atrophy. This approach may overcome peptide dosing limitations by enabling sustained endogenous protein production.
circRNA · WO 2025Site-Specific GLP-2 Immunoglobulin Fc Conjugates
Hanmi Science Co., Ltd. (South Korea) has developed site-specific GLP-2 conjugates linking native GLP-2 or a derivative via a non-peptidic polymer to an immunoglobulin Fc fragment, attached to a C-terminally introduced sulfhydryl group rather than the N-terminal amine. Retrieved results claim significantly increased GLP-2R binding affinity, extended in vivo half-life, and improved in vivo persistence and stability.
CN Patents Active 2019 & 2023GLP-2 Analog Dimers (Disulfide-Bridged)
Tianjin Institute of Pharmaceutical Research discloses GLP-2 analog dimers in which two identical or different GLP-2 analog monomers are linked via intermolecular cysteine disulfide bonds, synthesized by Fmoc solid-phase peptide synthesis. Retrieved results claim in vivo half-lives of 8–96 hours — dramatically extended versus native GLP-2 (~7 min) or teduglutide (~2 h).
8–96 hr half-life claimVisualising the SBS GLP-2 Innovation Landscape
Key data signals extracted from patent literature via PatSnap Eureka — assignee activity, modality development stage, and clinical translation signals.
Assignee Patent Filing Activity — SBS GLP-2 Space
Zealand Pharma A/S leads with 25+ distinct filings across 12+ jurisdictions, followed by Shire-NPS/Takeda and Hanmi Science.
GLP-2 Modality Development Stage Distribution
Only two modalities have clinical data — approved teduglutide and Phase 3 glepaglutide/apraglutide. Five remain at preclinical or early IP stage.
GLP-2 Combination & Next-Generation Strategy Filing Timeline
Patent filing activity for combination approaches and novel formats shows accelerating innovation from 2019 onward, with circRNA and multi-hormone strategies emerging in 2023–2025.
GLP-2 Analog Drug Pipeline: Compound-Level Comparison
Key compounds, assignees, structural approach, and development stage — derived exclusively from patent literature retrieved via PatSnap Eureka.
| Compound | Assignee | Key Structural Feature | Half-Life | Stage | Indication |
|---|---|---|---|---|---|
| Teduglutide (Gattex/Revestive) | NPS Allelix → Shire → Takeda | Ala2→Gly DPP-IV resistance | ~2 hours | Approved | SBS (PN-dependent) |
| Glepaglutide (ZP1848) | Zealand Pharma A/S | Multi-position substitutions (8, 16, 24, 28); C-terminal deletions | Weekly dosing | Phase 3 | SBS — EASE SBS 1 & 2 |
| Apraglutide | VectivBio AG | Optimized dosing regimen; long-acting GLP-2 analog | Extended | Phase 3 | SBS — dosing regimen WO 2025 |
| GLP-2 Peptibody (B264/K274) | Shire-NPS / Takeda | GLP-2–Fc immunoglobulin fusion (SEQ ID NO: 2–16) | Extended beyond ~2 h | Preclinical | SBS, ECF, GI radiation, obstructive jaundice |
| Site-Specific Fc Conjugate | Hanmi Science Co., Ltd. | Non-peptidic polymer via C-terminal sulfhydryl | Extended | Preclinical | SBS, IBD |
| GLP-2 Dimers | Tianjin Institute of Pharmaceutical Research | Intermolecular cysteine disulfide bridge (Fmoc SPPS) | 8–96 hours | Preclinical | SBS |
| Lipophilic GLP-2 Derivatives | Novo Nordisk A/S | Fatty acid chain on internal residues (S5, S7, D8…) | Protracted (depot-like) | Preclinical | SBS and GI disorders |
| circRNA GLP-2 | Miller, Russell (individual) | Circular polyribonucleotide + half-life extension moiety | Sustained (endogenous production) | Early IP | SBS, SBS-IF, pediatric SBS, TPN atrophy |
Need competitive intelligence on GLP-2 biosimilar entrants?
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Combination Approaches & Next-Generation Strategies
The patent landscape reveals five distinct combination and next-generation strategies beyond single-target GLP-2 analog optimization — signalling where competitive differentiation is heading.
GLP-2 + Insulinotropic Peptide (GLP-1/GIP)
Hanmi Pharm. Co., Ltd. files from 2023 (IL, pending) specifically claim combination therapy of an insulinotropic peptide (GLP-1, GIP, or analogs thereof) with GLP-2 for preventing or treating SBS. A separate Hanmi filing (CN, 2025, pending) extends this to combination with TNFα inhibitors for inflammatory bowel disease indications. Signals suggest Hanmi is positioning a multimodal gut hormone combination as a next-generation intestinal rehabilitation strategy.
Perioperative GLP-2 Administration
The Shire-NPS/Takeda patent family (WO, CA, IN, JP, TW, MX, AU, BR, CN jurisdictions) covers administration of GLP-2 analogs and GLP-2 peptibodies before, during, or after surgical small bowel resection — an emerging preemptive/perioperative rehabilitation strategy distinct from post-resection chronic therapy. This represents a potentially important prophylactic indication for patients with colon-in-continuity with remnant small intestine.
GLP-2 + IGF-1 / Growth Hormone Co-Administration
1149336 Ontario Inc. patents describe synergistic proliferative effects on upper and lower GI tissue when GLP-2 is co-administered with IGF-1, IGF-2, or growth hormone, claiming enhanced bowel growth compared to any agent alone. This signals a historical combination rationale that may re-emerge in modern intestinal rehabilitation protocols.
GLP-2 and Microbiome/Prebiotic Strategies
One filing in the dataset (Prolacta Bioscience/Probiogen; CN, 2022) references GLP-2's role in reducing intestinal permeability through prebiotic-driven endogenous GLP-2 secretion from L cells in the context of SBS, IBD, and IBS — signaling interest in indirect GLP-2 pathway activation via gut microbiome modulation as a complementary or adjunct approach.
Who Owns the GLP-2 SBS Patent Landscape?
Zealand Pharma A/S (Denmark) is by far the most prolific assignee in this dataset, with at least 25 distinct patent filings across AU, CA, CO, EP, IL, JP, MX, SG, TW, US, WO, BR, NZ jurisdictions. Their portfolio covers glepaglutide/ZP1848 chemical structure, dosing regimen optimization, PS-volume adjustment algorithms, and EASE SBS clinical trial-derived medical uses. Zealand Pharma's filings extend through 2025, representing the most temporally current IP position in the field. For full landscape analysis, PatSnap's IP analytics tools can map the complete portfolio.
Shire-NPS Pharmaceuticals / Takeda Pharmaceuticals represent the original teduglutide developer lineage, reflecting the 2016 Shire acquisition of NPS Pharmaceuticals and the 2019 Takeda acquisition of Shire. Their filings cover GLP-2 Fc-fusion proteins, peptibodies, and perioperative administration strategies across CA, IN, WO, JP, TW, MX, BR, AU jurisdictions.
Hanmi Pharm. Co., Ltd. / Hanmi Science Co., Ltd. (South Korea) are active filers for site-specific GLP-2–Fc conjugates and combination therapy of GLP-2 with insulinotropic peptides, with active CN patents and pending IL patents through 2023–2025. VectivBio AG (Switzerland) filed the most recent assignee-specific SBS patent in this dataset (WO, 2025) covering apraglutide dosing regimens. Enzene Biosciences Limited (India) represents emerging biosimilar/generic GLP peptide chemistry activity from South Asian players, with an AU filing in 2025. For life sciences IP intelligence across all these players, the PatSnap life sciences solutions platform provides dedicated tools.
The foundational academic GLP-2 biology originates from 1149336 Ontario Inc. — a holding entity associated with Dr. Daniel J. Drucker's laboratory at the University of Toronto — whose patents cover GLP-2 therapeutic use, upper GI applications, and GLP-2/IGF-1 combination approaches. According to NIH-supported research and EMA regulatory filings, GLP-2 receptor biology underpins the entire therapeutic rationale for this drug class.
Short Bowel Syndrome GLP-2 Pipeline — key questions answered
Short bowel syndrome (SBS) is a rare, life-threatening malabsorption disorder resulting primarily from surgical resection of the small intestine, leaving patients dependent on parenteral nutrition (PN) or parenteral support (PS) for survival. GLP-2 receptor agonists promote intestinal mucosal growth and adaptive rehabilitation, addressing the root cause of malabsorption by stimulating crypt stem cell proliferation, villus elongation, and increasing mucosal surface area.
Several results note an estimated prevalence of at least 40 SBS patients per million population requiring home parenteral nutrition for non-malignant disease.
The pipeline includes teduglutide (approved as Gattex/Revestive), glepaglutide/ZP1848 (Zealand Pharma, Phase 3 EASE SBS 1 and EASE SBS 2 trials), and apraglutide (VectivBio AG, 2025 WO filing). Next-generation formats include GLP-2 fusion proteins, site-specific Fc conjugates, disulfide-bridged dimers, lipophilic derivatives, and circular RNA-encoded GLP-2 biologics.
Glepaglutide (ZP1848), developed by Zealand Pharma A/S, incorporates multiple substitutions relative to [hGly2]GLP-2 at positions 8, 16, 24, and/or 28, optionally with deletions at positions 31–33 and N/C-terminal stabilizing sequences, to achieve improved chemical stability in liquid formulation. It has been evaluated in Phase 3 EASE SBS 1 and EASE SBS 2 trials, where a subpopulation of patients achieved complete independence from parenteral support — described as the first results in placebo-controlled trials showing PS independence is achievable in a subset of patients.
Hanmi Pharm. Co., Ltd. files from 2023 specifically claim combination therapy of an insulinotropic peptide (GLP-1, GIP, or analogs thereof) with GLP-2 for preventing or treating SBS. A separate Hanmi filing (CN, 2025) extends this to combination with TNFα inhibitors for inflammatory bowel disease indications. Earlier patents from 1149336 Ontario Inc. describe synergistic proliferative effects when GLP-2 is co-administered with IGF-1, IGF-2, or growth hormone.
Zealand Pharma A/S holds the most geographically comprehensive and temporally recent GLP-2 analog IP position in this dataset, with at least 25 distinct patent filings across AU, CA, CO, EP, IL, JP, MX, SG, TW, US, WO, BR, NZ jurisdictions covering GLP-2 analog chemical structure (glepaglutide/ZP1848 series), dosing regimen optimization, PS-volume adjustment algorithms, and EASE SBS clinical trial-derived medical uses.
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References
- GLP-2 analogs and peptibodies for administration before, during or after surgery — Shire-NPS Pharmaceuticals, Inc., 2019, CA [Patent]
- GLP-2 analogs and peptibodies for administration before, during or after surgery — Takeda Pharmaceutical Company Limited, 2020, AU [Patent]
- Intestinotrophic glucagon-like peptide-2 analogs — NPS Allelix Corp., 2001, US [Patent]
- Glucagon-like-peptide-2 (GLP-2) analogues and their medical uses for the treatment of short bowel syndrome (SBS) — Zealand Pharma A/S, 2024, WO [Patent]
- Dosage regimens for glucagon-like peptide 2 (GLP-2) analogs — VectivBio AG, 2025, WO [Patent]
- Circular polyribonucleotides encoding glucagon-like peptide 2 (GLP-2) and uses thereof — Miller, Russell, 2025, WO [Patent]
- Combination therapy of insulinotropic peptide and GLP-2, for preventing or treating short bowel syndrome — Hanmi Pharm. Co., Ltd., 2023, IL [Patent]
- Glucagon-like peptide-2 (GLP-2) analogs and their medical use for the treatment of short bowel syndrome (SBS) — Zealand Pharma A/S, 2026, JP [Patent]
- GLP-2 fusion polypeptides and uses for treating and preventing gastrointestinal conditions — Shire-NPS Pharmaceuticals, Inc., 2022, JP [Patent]
- Site-specific GLP-2 conjugates using immunoglobulin fragments — Hanmi Science Co., Ltd., 2023, CN [Patent]
- GLP-2 analog dimers and their preparation methods and applications — Tianjin Institute of Pharmaceutical Research, 2014, CN [Patent]
- NIH: GLP-2 receptor biology and intestinal mucosal growth — National Institutes of Health
- European Medicines Agency — Revestive (teduglutide) regulatory information
- World Health Organization — Rare disease classification and prevalence data
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform. Patent landscape data represents a snapshot of innovation signals within the retrieved dataset only and should not be interpreted as a comprehensive view of the full field, clinical pipeline, or regulatory landscape.
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